BACKGROUND:Diffuse axonal injury is a common consequence of traumatic brain injury (TBI) and often co-occurs with hypoxia, resulting in poor neurological outcome for which there is no current therapy. Here, we investigate the ability of the multifunctional compound erythropoietin (EPO) to provide neuroprotection when administered to rats after diffuse TBI alone or with post-traumatic hypoxia.METHODS:Sprague-Dawley rats were subjected to diffuse traumatic axonal injury (TAI) followed by 30minutes of hypoxic (Hx, 12% O2) or normoxic ventilation, and were administered recombinant human EPO-alpha (5000IU/kg) or saline at 1 and 24hours post-injury. The parameters examined included: 1) behavioural and cognitive deficit using the Rotarod, open field and novel object recognition tests / 2) axonal pathology (NF-200) / 3) callosal degradation (hematoxylin and eosin stain) / 3) dendritic loss (MAP2) / 4) expression and localisation of the EPO receptor (EpoR) / 5) activation/infiltration of microglia/macrophages (CD68) and production of IL-1beta.RESULTS:EPO significantly improved sensorimotor and cognitive recovery when administered to TAI rats with hypoxia (TAI+Hx). A single dose of EPO at 1hour reduced axonal damage in the white matter of TAI+Hx rats at 1day by 60% compared to vehicle. MAP2 was decreased in the lateral septal nucleus of TAI+Hx rats / however, EPO prevented this loss, and maintained MAP2 density over time. EPO administration elicited an early enhanced expression of EpoR 1day after TAI+Hx compared with a 7-day peak in vehicle controls. Furthermore, EPO reduced IL-1beta to sham levels 2hours after TAI+Hx, concomitant to a decrease in CD68 positive cells at 7 and 14days.CONCLUSIONS:When administered EPO, TAI+Hx rats had improved behavioural and cognitive performance, attenuated white matter damage, resolution of neuronal damage spanning from the axon to the dendrite, and suppressed neuroinflammation, alongside enhanced expression of EpoR. These data provide compelling evidence of EPO's neuroprotective capability. Few benefits were observed when EPO was administered to TAI rats without hypoxia, indicating that EPO's neuroprotective capacity is bolstered under hypoxic conditions, which may be an important consideration when EPO is employed for neuroprotection in the clinic.

The overall aim of this thesis was to describe occupational therapy practice for clients with cognitive impairment following acquired brain injury (CIABI) from the perspective of practicing occupational therapists (OTs). To fulfill this aim, qualitative and quantitative approaches were used including interviews (Study I) and questionnaires (Studies II -IV). Based on the qualitative descriptions generated in Study I, a questionnaire was developed and evaluated for content validity and test-rest validity (Study II). The questionnaire was then used in a survey (Study III). The reactive Delphi technique was used to empirically define the aspects that OTs found to be consistent with the concept of therapeutic use of self (Study IV). The results showed that a predominant practice pattern was the use of ADL activities for intervention regardless of whether limitations in occupational performance or cognitive function were assessed, or whether the approach to therapy was remedial or compensatory. General ADL-instruments were used more than instruments focused on impairment level. Therapies covering a wide range of cognitive impairments, and abilities important to organizing and executing occupational performance were commonly targeted. Therapies targeting clients’ activity limitations were prioritized before remediating impairment. Therapeutic use of self was regarded as being important and the results identified clientspecific aims not earlier described in relation to therapeutic use of self. Another prominent practice pattern was the collaborative approach toward clients, relatives, and other staff. Theories used to support practice were primarily general. Occupational therapy practice for clients with CIABI was found to be complex, and the practice patterns were affected by circumstances such as the ‘hidden’ nature of the cognitive impairments, perceived lack of knowledge, and organizational issues. The results of this thesis can be used as a foundation for further research on practice patterns or the specific therapies used. It can facilitate discussions on strengths and weaknesses witcurrent practice, the need for development, and research utilization.

Total body irradiation is the irradiation of the entire patient as a conditioning for bone marrow transplants. The conditioning process involves destroying the bone marrow allowing for repopulation of the donor bone marrow cells, suppression of the immune system to allow stop graft rejection, and to eliminate the cancer cell population within the patient. Studies have been done demonstrating the importance of TBI conditioning for BMT5. A range of TBI treatment techniques exist, this department uses a bi-lateral technique which requires bolus packed around the patient to simplify the geometry of the treatment. This investigation will focus on one technique which involves using a translating bed. This technique effectively scans a radiation beam over the patient as the bed moves through the beam. Other investigations on translating beds concentrated on varying the scan speed to achieve a dose uniformity to within ±5%. The recommendations quote a dose uniformity of +5% and -10% as acceptable⁹. The dose uniformity in these investigations was along the midline in the longitudinal direction only. This investigation varied field size to achieve dose uniformity to within ±2.5% along the midline of an anthropomorphic phantom. The goal was to determine if a dynamic multi-leaf collimator could be used to give a uniform in the transverse direction as well as the longitudinal direction. An advantage of utilizing the DMLC for this treatment is the ability to shield organs at risk, i.e. lungs and kidneys, without requiring resources to produce shielding blocks14. Gafchromic-EBT film18 was used as a dosimeter but gave unreliable results due to the lack of film scanning equipment with an appropriate sensitivity for reading the dose to the film. Scans were simulated using Xio treatment planning software. The results from the simulations gave a more reliable indication of the absorbed dose to the midline of the phantom. The disadvantage of this varying field size technique was the time and complexity involved in creating a treatment plan. Within the Xio software exists a limit on the number of beams allowed to be applied in a single plan. There is a maximum of 99 beams allowed which is not enough for complete coverage of a patient. A way around this is to increase the field sizes and decrease the scan speed. This option was not investigated. The advantage of this technique was the increased dose uniformity (±2.5%) in comparison to the varying scan speed techniques (±5%). This technique also allows the patient to be unencumbered during the treatment making the process more comfortable for them.

The lived experiences of the family of a Traumatic Brain Injury (TBI) survivor is an under represented, yet growing field of qualitative psychological research. This thesis used a case study approach with a family in which one member sustained TBI thirteen years previously. Using conversational unstructured interview techniques, I participated with the family in eliciting public narratives around their experiences since the accident. These public stories were also thickened by individual interviews, which both supported and contradicted the public narratives. In the analysis I found two major narrative lines, the first of which was the baby-narrative which held that the injured person must not be injured any further in word or deed and must be protected at all time. The second dominant narrative was the fighting-narrative, which was characterised by language and actions around fighting/battling on behalf of the injured person against uncaring ‘others’. Several important suppressed or counter narratives emerged during the individual interviews, which could not be spoken about publically. I conclude that the power of the two dominant narratives is fuelled by constant rehearsal and enactment, which actually freezes the family and does not allow it to move forward. Suppressed stories are discussed as a possible avenue for therapeutic growth and for the evolution of the family story as they age.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Motor vehicle accidents involving pedestrians are some of the most common and lethal forms of injury for children in the United States. Among younger children, a common mechanism of action for severe trauma is when a vehicle runs over the child in a forward or backward motion at low speed resulting in a blunt crush injury. This typically occurs in non‐traffic settings including driveways, sidewalks, and roadways. Such incidents have been referred to in many different ways in the literature but for the purposes of this paper will be referred to as low speed vehicle run‐overs. This is a retrospective chart review carried out at Phoenix Children’s Hospital in affiliation with the University of Arizona College of Medicine‐Phoenix that categorizes and examines the injuries sustained by patients involved in low speed vehicle runovers occurring between December 2007 and August 2013. Fifty‐five pediatric patients were included with a median age of 24 months and 6 of these patients were fatally injured. Internal injuries were common overall and significantly more common in children ≤24months. Over half of the cohort sustained fractures, with a 24% incidence of skull fractures. All fatalities were the result of traumatic brain injury. Twenty percent of victims required operative intervention. It was concluded that the severity of these types of incidents varies from minimal to life threatening and best care requires close and thorough evaluation by the trauma and emergency department teams.

Aside from preventing traumatic brain injuries (TBIs) altogether, treatment options for TBI typically focus on the secondary biochemical processes that occur in response to the primary mechanical insult. These secondary injuries can lead to apoptosis and necrosis in the days and weeks that follow a TBI. Therefore, finding a treatment that can prevent, reduce, and repair secondary damage is instrumental in the recovery of TBI patients. The flavonoid 7,8-dihydroxyflavone (7,8-DHF) has been identified as a TrkB agonist that mimics the effects of brain derived neurotrophin factor (BDNF). Upon binding to the TrkB receptor, signaling cascades are initiated that can promote neuronal survival and neural differentiation. The use of 7,8-DHF in the treatment of TBI is favorable due to its long half-life and ability to pass the blood-brain barrier (BBB). In this study, we evaluated the dosage time frame of 7,8-DHF that would allow for the greatest impact in recovery after a focal TBI. Adult Sprague-Dawley rats were subjected to a moderate cortical impact injury and administered a 5mg/kg dose of 7,8-DHF i.p. for five days starting on day 0, 2, 3, or 5 post injury. Sensorimotor function was evaluated with beam walk and rotarod test. Morris Water Maze (MWM) and fear conditioning test were used to analyze cognitive function. Biotinylated dextran amine (BDA) was injected into the contralateral cerebral cortex 14 days after injury and animals were sacrificed 28 dpi. Brain sections were processed for Giemsa histological staining to assess cortical lesion volume and the total number of surviving neurons. Parallel sections were processed for BDA staining to assess changes of axon sprouting in the injured cortex. VGlut-1 staining of the hippocampus was used to identify presynaptic plasticity. We found that the administration of 7,8- DHF starting at one hour after TBI could provide protection against motor and cognitive dysfunction. Histological examination showed a significant reduction of cortical lesion volume and higher number of survival neurons in the injured hippocampus when 7,8-DHF administration began one hour and two days after injury. BDA staining of intracortical axon sprouting and VGlut-1 staining of the hippocampus highlighted a trend that 7,8-DHF administration starting day five post brain injury may enhance neuronal plasticity. Collectively, the results indicate that 7,8-DHF can provide the better neuronal protection when administration begins one hour after TBI.

Recent applications of medical imaging, advanced polymers, and composites have led to the development of new equipment for athletes and soldiers. A desire to understand the performance of headgear that resists impacts ongoing since the 1970’s has found more traction in recent years with the usage experimental models that have a greater degree of bio-fidelity. In order to determine which features of helmets from different sports (Soccer, Lacrosse, Football, and Hockey) were tested on a Hybrid III 50th Percentile Male headform with an accelerometer rig at the center of mass.Testing was performed by administering impacts to the headform with an impulse hammer that provides transient force data in order to quantify inputs and outputs of the system to develop a non-dimensional transfer function. Helmet performance is compared by sport worn in order to determine desirable manufacturing features and develop prototype helmets that outperforms current athletic equipment.

Background: Childhood Traumatic Brain Injury (TBI) has been identified as a crucial public concern, causing interrup-tion in children’s cognitive development, sometimes resulting in permanent impairment or even death. Hence documen-tation in health and school records regarding their functioning or environmental restrictions post injury, seems vital for the facilitation of communication between a child’s systematic and ongoing environment. Especially since children’s health has been described as a holistic construct comprised of psycho, social and physical well-being. Requiring continual inter-disciplinary and collaborative efforts over their course of development. Aim: To explore literature related to cognitive functioning and recommended support for children who have experienced a TBI, and how professional’s document their associated problems within medical and school records regarding activities in or outside the classroom. Method: A sys-tematic review, strictly comprised of empirical studies. Selected due to its sequential structural design for attainment of literature relevant to the research topic of choice and quality assessment procedures which enable reduction of threats to bias findings. Results: A total of 9 articles were yielded after quality assessment and depicted that. Reduced processing speeds in cognitive ability domains can be regarded as the default or baseline outcomes after a childhood TBI. Predictors within these different domains impacted their adequate academic, social function and varied depending on age at injury (2-4yrs or 4-8yrs), Injury severity (mild, moderate/severe), family function and time points. Early and severe TBI showed significant residual impairments across all time points, whilst the mild to moderate groups showed low to average func-tioning, as with the typical sample groups after two-year time points. Executive, attention skills impairment and post injury support within home and school settings. Showed to have the highest impact on both behaviours in, outside the classroom and academic performance. Documentation: Mainly biological and admission details were documented in the medical records. Within school records, all except one most recent study used either parental, teacher reports or direct measures to assess functioning of TBI affected children within school. Hereby a need for documentation of environmental factors within medical records, high quality transition of their TBI information within their school settings and continual docu-mentation of their progress or supports in school is required.

Pneumonia is the second leading cause of disability-adjusted life-years lost worldwide and the eighth leading cause of death in the United States. Traumatic brain injury (TBI) patients have classically been considered immunosuppressed, but recent research reported that mild head trauma patients have reduced incidence of pneumonia compared to blunt trauma patients. Using our mild TBI model followed by bacterial pneumonia, we investigated the effect of neuronal signaling on innate immune function. To test whether any mild injury primes host immune responses to pneumonia, we generated a mild tail trauma (TT) model. mTBI mice showed protection from bacterial pneumonia while TT mice did not. Using an FDA-approved neurokinin-1 receptor (NK1R) antagonist, aprepitant, we confirmed our previous findings that substance P (SP) is a key mediator of enhanced resistance to pneumonia. Blocking NK1R showed that mTBI-induced release of SP augments pulmonary neutrophil recruitment and microbicidal activity to pulmonary bacterial pathogens. In TT mice, NK1R agonism enhanced the same neutrophil functions, further supporting the hypothesis. No differences were found between mTBI and TT neutrophils’ ability to phagocytose, generate oxidative burst, or acidify phagosomes. However, neutrophils from mTBI mice produced more neutrophil extracellular traps in response to bacterial challenge. These studies show that neurokinin signaling in our model contributes to enhanced bacterial clearance. Cholinergic anti-inflammatory pathway signaling though the α7 nicotinic acetylcholine receptor (α7 nAChR) is also a critical component of improved survival. Blockade of α7 nAChR abrogated the mTBI survival benefit. Mimicking cholinergic signaling using α7 nAChR agonist recapitulated the mTBI reduced pro-inflammatory cytokine production and improved survival. No physiologic differences emerged within 24h following pneumonia, but mTBI and α7 agonist treated mice had significantly lower TNFα in bronchoalveolar fluid, suggesting reduced injurious pulmonary inflammation. However, replacing early TNFα during pneumonia did not increase mortality. Western blot analysis showed downregulation of HMGB1 release in mTBI mice, suggesting that vagal cholinergic signaling reduces late mediators of organ damage. Our experiments show that mTBI enhances resistance to pneumonia by activating the vagus nerve signaling through neurokinin and cholinergic pathways. Translation of these findings could be innovative solutions to fighting or preventing infections.

Made available in DSpace on 2016-04-28T20:39:31Z (GMT). No. of bitstreams: 1 Carolina Gonzaga Sanches Jorquera.pdf: 277124 bytes, checksum: 4d8602ef0dbe4f4a8ed4977768ad5580 (MD5) Previous issue date: 2007-09-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / TBI is defined as trauma in the encephalon from an external physical force that can result in a compromised motor, cognitive, emotional and/or change in behaviour. The most distinct element in TBI is a change in neuronfunctioning in relation to family and the community, both which undergo important reorganization and adaptation. The objective of this study was to identify and understand the commonalities and the specifics modification in living style and explore the effects of TBI through a case study a family with adolescent children who sustained TBI four years ago. Individual meetings were held with relatives, as well as a meeting with the immediate family to investigate the following: progression (of the injury) impact, perception and procurement of a support network. It was possible to identify that until the accident occurred, it was a close-knit family with good communication and relationship. The hospitalization phase resulted in a different perception (security vs. hopelessness), communication between individuals ceased to be as effective, with subsequent feelings of abandonment and being disconnected. The daughters were mourning theirs losses and the mother was concerned about maintaining a daily life style. Upon returning home, it was identified that the healthy spouse started to take on few new roles. The daughter, facing the adolescence, lost the ability for differentiated. When it became clear that full recovery of all symptoms was impossible, the relatives began to mourn the victim. Currently, they are all trying to return to former goals, even though the victim considers himself retired, focusing on successes, not failures. Finally, we conclude that even though it was a family with good cognitive and social resources, the illness caused a significant crisis that took four years before the family could find a new lease on life and try to carry on / Define-se o TCE como uma agressão ao encéfalo por força física externa que pode resultar em comprometimento motor, cognitivo, emocional e/ou mudanças no comportamento. O diferencial do TCE está nas alterações neurocomportamentais que exigem da família e rede de convivência próxima, importantes reorganizações e adaptações. O objetivo do presente trabalho foi identificar e compreender as comunalidades e especificidades na vivência e elaboração de um TCE tendo-se optado pela realização de estudo de caso de uma família com filhos adolescentes cujo provedor passara por um TCE havia quatro anos. Foram realizados encontros individuais com os familiares e um encontro com a família investigando: fases do adoecimento, impacto, crenças, rede de suporte encontrada. Foi possível identificar que até o momento do acidente, constituíam uma família coesa, com comunicação efetiva e bons vínculos. A fase de hospitalização suscitou diferentes percepções (segurança X desamparo), na qual a comunicação entre membros já não era tão eficaz, proporcionando sentimento de abandono e não coesão. As filhas se focavam nas perdas e a mãe nas realizações práticas que mantinham o funcionamento do sistema. No retorno para casa, identificou-se que o cônjuge saudável não tinha mais o parceiro e ganhou uma série de novas funções. As filhas perdem a base sólida para o processo de diferenciação, característico da fase do ciclo vital da adolescência. Com a consciência de que não haveria remissão total dos sintomas, os familiares entram em contato com o luto da figura perdida. Atualmente, verificou-se que todos estão tentando retomar os planos individuais, inclusive a figura adoecida que definiu para si o papel de aposentado, a partir do qual mantém o foco no que ganha e não no que perde. Enfim, pode-se concluir que mesmo se caracterizando por uma família com bons recursos cognitivos e sociais, o adoecimento causou uma importante crise e que, levou quatro anos para que os familiares começassem a dar um novo sentido à vida para tentarem seguir em frente